反应详情

温度

25 °C

To a solution of chlorosulfonylisocyanate (28 μl, 0.32 mmol) in dichloromethane (3 mL) was added benzyl alcohol (28 μl, 0.27 mmol). The reaction was stirred at 25° C. for 30 min. A solution of (1R,2S,7R,8S)-5-(7-aminomethyl-1,1-dioxo-1,4-dihydro-1λ6-thieno[2,3-e][1,2,4]thiadiazin-3-yl)-3-(4-fluoro-benzyl)-6-hydroxy-3-aza-tricyclo[6.2.1.02,7]undec-5-en-4-one (prepared as described in Example 33f; 0.10 g, 0.21 mmol) and triethylamine (125 μl, 0.90 mmol) in dichloromethane (3 mL) was then added to the above solution via cannula. The reaction was stirred at 25° C. for 1.5 h. The mixture was diluted with dichloromethane (10 mL) and washed with 1.0 M aqueous hydrochloric acid solution (10 mL). The organic was dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was purified via flash column chromatography (Teledyne Isco RediSep column; 0-3% methanol in dichloromethane) to afford the desired product, benzyl (N-{3-[(1R,2S,7R,8S)-3-(4-fluoro-benzyl)-6-hydroxy-4-oxo-3-aza-tricyclo[6.2.1.02,7]undec-5-en-5-yl]-1,1-dioxo-1,4-dihydro-1λ6-thieno[2,3-e][1,2,4]thiadiazin-7-ylmethyl}amino)sulfonylcarbamate (0.13 g, 0.18 mmol, 86%), as a white solid. 1H NMR (400 MHz, CDCl3) δ: 1.19-1.77 (6H, m), 2.57-2.58 (1H, m), 2.83-2.88 (2H, m), 3.46 (1H, m), 4.22 (1H, d, J=15.6 Hz), 4.50 (2H, bs), 5.12-5.18 (3H, m), 6.06 (1H, bs), 7.02-7.07 (3H, m), 7.19-7.23 (2H, m), 7.33-7.39 (5H, m).

1. stirringThe reaction was stirred at 25° C. for 1.5 h
2. washwashed with 1.0 M aqueous hydrochloric acid solution (10 mL)
3. dry with materialThe organic was dried over magnesium sulfate
4. filtrationfiltered
5. concentrationconcentrated in vacuo
6. customThe residue was purified via flash column chromatography (Teledyne Isco RediSep column; 0-3% methanol in dichloromethane)